Inherited hearing impairment affects about 1 in 2000 newborns. Up to 50 percent of all patients with autosomal recessive nonsyndromic prelingual deafness in different populations have mutations in the gene encoding the gap-junction protein connexin 26 (GJB2) at locus DFNB1 on chromosome 13q12. However, a large fraction (10 to 42 percent) of patients with GJB2 mutations have only one mutant allele; the accompanying mutation has not been identified. DFNB1-linked familial cases with no mutation in GJB2 have also been reported.

In many populations, up to 50% of all cases of ARNSHI are caused by mutations in the DFNB1 locus (MIM 220290) on 13q12.⁴ This locus contains the GJB2 gene (MIM 121011), encoding connexin-26 (Cx26),⁵ which belongs to a family of transmembrane proteins with about 20 members in humans. Hexamers of connexins (connexons) are displayed in the plasma membrane. Docking of connexons on the surfaces of two adjacent cells results in the formation of intercellular gap junction channels.⁶ Several different connexins, including Cx26, have been shown to participate in the complex gap junction networks of the cochlea.^{7, 8} It has been postulated that these networks play a key role in potassium homeostasis, which is essential for the sound transduction mechanism.⁹